Functional crosstalk between T cells and monocytes in cancer and atherosclerosis

Abstract

Monocytes and monocyte‐derived cells, including Mϕs and dendritic cells, exhibit a diverse array of phenotypic states that are dictated by their surrounding microenvironment. These cells direct T cell activation and function via cues that range from being immunosuppressive to immunostimulatory. Solid tumors and atherosclerotic plaques represent two pathological niches with distinct immune microenvironments. While monocytes and their progeny possess a phenotypic spectrum found within both disease contexts, most within tumors are pro‐tumoral and support evasion of host immune responses by tumor cells. In contrast, monocyte‐derived cells within atherosclerotic plaques are usually pro‐atherogenic, pro‐inflammatory, and predominantly directed against self‐antigens. Consequently, cancer immunotherapies strive to enhance the immune response against tumor antigens, whereas atherosclerosis treatments seek to dampen the immune response against lipid antigens. Insights into monocyte‐T cell interactions within these niches could thus inform therapeutic strategies for two immunologically distinct diseases. Here, we review monocyte diversity, interactions between monocytes and T cells within tumor and plaque microenvironments, how certain therapies have leveraged these interactions, and novel strategies to assay such associations.

Induction of Cytokines by Nucleic Acid Nanoparticles (NANPs) Depends on the Type of Delivery Carrier

“…The cytokine data ( Figures 5 and 6) correlate with NANP uptake by immune cells, which was studied by flow cytometry (Figure 7). The greater rates of NANP uptake by monocytes are consistent with the well-known phagocytic function of these cells [65]. The uptake of naked NANPs is negligible, which explains the lack of cytokine induction by RNA and DNA cubes used without a carrier.…”

Updating concepts on atherosclerotic inflammation: From pathophysiology to treatment

“…15 Beside phagocytic action, macrophages secrete pro-inflammatory cytokines, particularly interleukin (IL)-1β, IL-6, IL-12 and tumour necrosis factor-α (TNFα), that enhance the expression of CAMs on the surface of endothelium, and acquire the capacity of antigen presentation and also proliferate. 5,14,16,17 Increased expression of CAMs amplifies the infiltration of leucocytes, including T CD4 + lymphocytes, which are recruited through the CXC superfamily chemokines (eg, CXCL-9, CXCL-10 and CXCL-11). Inside the plaque, T cells are activated through antigen presentation and achieve a pro-inflammatory profile Th1.…”

“…The earliest recruited population are classical monocytes (CD16+/CD14‐), expressing the C‐C motif chemokine receptor‐2 (CCR‐2), CCR‐5 and C‐X‐C motif chemokine 3 receptor‐1 (CXC3R‐1) 12,13 . Recruitment of ‘nonclassical’ monocytes inside the atherosclerotic plaque occurs later, and their role in the pathogenesis of atherosclerosis is still debated 14 . Inside the vascular wall, monocytes maturate into macrophages and express scavenger receptors for lipoproteins, such as scavenger receptor A (SR‐A) and CD36, achieving the ability to internalize modified lipoproteins, particularly oxidized LDL particles.…”

“…Through phagocytosis of lipid particles, macrophages develop the peculiar phenotype of formation of the necrotic core of the atherosclerotic plaque 15 . Beside phagocytic action, macrophages secrete pro‐inflammatory cytokines, particularly interleukin (IL)‐1β, IL‐6, IL‐12 and tumour necrosis factor‐α (TNF‐α), that enhance the expression of CAMs on the surface of endothelium, and acquire the capacity of antigen presentation and also proliferate 5,14,16,17 . Increased expression of CAMs amplifies the infiltration of leucocytes, including T CD4 + lymphocytes, which are recruited through the CXC superfamily chemokines (eg, CXCL‐9, CXCL‐10 and CXCL‐11).…”

T Cells in Autoimmunity-Associated Cardiovascular Diseases

“…Moreover, adoptive transfer of effector T cells promotes atherogenesis in murine models, whereas transfer of regulatory T (Treg) cells is protective (8)(9)(10). Taken together, these and other studies clearly establish that T cell-mediated immunity is a major modulatory of atherosclerotic CVD pathogenesis (2,(11)(12)(13).…”